Interaction of B and T lymphocyte subsets with high endothelial venules in the rat: binding in vitro does not reflect homing in vivo

Lymphocytes continuously migrate through the body, and their efficient extravasation from the blood via high endothelial venules (HEV) is essential for initiating an appropriate immune response. Most investigations have focused on the lymphocyte/HEV interaction in vitro. However, to what extent such systems reflect the situation in vivo is not known. It is also unclear whether lymphocyte subsets immigrate into the HEV in proportion to their presence in the blood, and whether import capacity is limited by the HEV. When rat mesenteric lymph node lymphocytes were incubated in vitro on cryostat sections, the well-known preferential binding of B lymphocytes to HEV of Peyer's patches (PP) and T cells to HEV of axillary lymph nodes (axLN) was observed (axLN vs. PP: B lymphocytes 21.2 ± 5.0% vs. 40.6 ± 11.0%, T lymphocytes 84.6 ± 6.3% vs. 56.5 ± 12.9%). However, when labeled mesenteric lymph node lymphocytes were injected and their location within the HEV was analyzed 15 min later, no preferential interaction was seen. After injection of labeled thoracic duct lymphocytes, the percentage of labeled cells among B and T lymphocytes in the blood was significantly different (4.4 ± 0.9% vs. 8.9 ± 3.6%), whereas that in HEV of axLN (19.0 ± 6.4% vs. 16.6 ± 6.0%) and PP (30.6 ± 6.1% vs. 33.9 ± 4.4%) was comparable. Although the number of injected lymphocytes was similar in magnitude to the total blood lymphocyte pool, after injection there was no increase in lymphocyte numbers in the HEV. Thus, the adhesion assay in vitro does not completely reflect immigration into HEV in vivo. In addition, our data suggest that both the availability of lymphocyte subsets in small venules and the immigration rate into HEV are actively regulated in vivo.     

Comparative dermal carcinogenesis of shale and petroleum-derived distillates

Ten test materials derived from petroleum or hydrotreated shale oils were applied 3 times/week for up to 105 weeks to the shaved skin of 25 male and 25 female C3H/HeN mice per group. Mineral oil and benzo(a) pyrene (0.15%) were control materials. Clinical observations were recorded during the study. At death, histopathologic examination was conducted on skin, internal organs and any gross lesions. Exposures to some materials were ended midway in the study due to severe irritation. Chronic toxicity of all materials was limited to inflammatory and degenerative skin changes. Significant increases over control incidence of skin tumors (squamous cell carcinoma and fibrosarcoma) occurred with both petroleum and shale-derived naphtha (21%, 50%), Jet A (26%, 28%), JP-4 (26%, 50%), and crude oils (84%, 54%). Severely hydrotreated shale oil and petroleum and shale-derived diesel distillates were not considered tumorigenic. Results indicate that toxicity of comparable petroleum and shale-derived fractions was qualitatively similar and confirm earlier findings that hydrotreating reduces or eliminates carcinogenicity of raw shale oil.     

Costs and benefits of routine follow-up after curative treatment for endometrial cancer

OBJECTIVE: To examine the costs of routine outpatient follow-up after curative treatment of endometrial cancer, and to determine whether this leads to early detection of recurrence or survival. The impact of specific disease characteristics on survival is examined. DESIGN: Retrospective chart review, and calculation of costs. SETTING: Ottawa Regional Cancer Centre-Civic Division (ORCC-C). PATIENTS: All 432 patients referred to the ORCC-C with endometrial cancer between 1982 and 1991 who received treatment with curative intent and who continued with routine follow-up. RESULTS: Cancer recurred in 50 patients (11.57%). There was no statistically significant difference in overall survival between patients with symptomatic and asymptomatic recurrences, or between those with recurrences detected during routine follow-up visits or in the interval between routine visits. Of 4830 Papanicolaou (Pap) smears performed routinely, cancer was detected in 6 cases. The mean cost of the routine follow-up procedures for each patient with a recurrence was $19,200. CONCLUSION: Intensive follow-up of women with endometrial cancer does not result in improved survival. A prospective randomized study is warranted to evaluate other potential benefits of follow-up, such as improved quality of life or decreased morbidity. There is no economic or clinical justification for the routine use of the Pap smear in the follow-up of patients with endometrial cancer. The potential benefits of routine follow-up in endometrial cancer and other types of cancer with favourable prognoses warrant critical evaluation.     

The state of DNA methylation in the promoter and exon 1 regions of the human gene for the interleukin-2 receptor {alpha} chain (IL-2R{alpha}) in various cell types

The gene for the human interleukin-2 receptor     

Effects of intravenous L-acetylcarnitine on retinal oscillatory potentials

L-acetylcarnitine is a compound with cholinergic properties and putative action on the visual system and the glucose metabolism. Ten healthy, emmertropic volunteers (age range: 21 to 28 years) were studied. Each subject was administered 5, 10, and 30 mg/kg acute intravenous doses of L-acetylcarnitine and matching placebo. Retinal oscillatory potentials to full-field flash stimulation were recorded before and 30, 60, and 120 min after administration. A systematic reduction of the implicit time of the P2 and N2 oscillatory potential components was observed after administration of the 10 and 30 mg/kg doses: significant changes were not evident at the 5 mg dose or after placebo. The latency reduction was significantly correlated with the postdrug increment of the L-acetylcarnitine plasma concentration. No other systematic modification in latency of amplitude was observed.The results were presented in part at the XXV I.S.C.E.V. Symposium, Sarasota (Florida), April 26–30, 1987.     

Identification of fast spurts of pyridine nucleotide oxidation evoked by light stimulation in the isolated perfused vertebrate retina

Transitory increases of ultraviolet transmission on stimulation with light were recorded simultaneously with electroretinogram on and off effects from isolated vertebrate retina. The spectral distribution of the optical light responses coincided with that of NADH reduction. The correlation of the optical, or respiratory, responses and the electrical responses were very close within a wide range of stimulus parameters, suggesting an interpretation in terms of supply and demand of energy with a tight coupling between the two kinds of evoked activity. Prerequisite to the response behaviour was the preservation of synaptic signal transmission from first- to higher-order retinal neurons.     

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.     

Analgesic profile of the sodium salt of pemedolac

Pemedolac Na, 1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)-pyrano [3,4-b] indole-1-acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED₅₀ values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall-Selitto model, the ED₅₀ o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ-induced writing in mice with an ED₅₀ of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley-Liss, Inc.